bims-aporos 2018-11-11 papers

Issue of 2018–11–11
four papers selected by
Gavin McStay, Staffordshire University

Food Chem Toxicol. 2018 Oct 31. pii: S0278-6915(18)30802-0. [Epub ahead of print]

Silk sericin induced pro-oxidative stress leads to apoptosis in human cancer cells.

Pro-oxidative stress induced by dietary polyphenols elevates reactive oxygen species (ROS) production in cancer cells, which subsequently leads to oxidative stress-mediated apoptosis. Sericin, a principal component of silk is associated with a mixture of polyphenols and flavonoids, possesses various biomedical attributes including anticancer activity. In the present study, we have evaluated the pro-oxidative effect of Bombyx mori sericin (BMS), Antheraea assamensis sericin (AAS), and Philosamia ricini sericin (PRS) against different cancer cells. Cytotoxicity of silk sericin (SS) evaluated using A431, SAS, and MCF-7 cells showed ≥50% reduction in their viability at 4 mg/mL. Intracellular ROS levels, cell cycle arrest, and apoptosis assessed using flow cytometry corroborated that SS treatment elevated the intracellular ROS levels, caused cell cycle arrest at the sub-G1 phase and resulted in apoptotic cell death. SS treated A431 and SAS cells showed upregulation of p53 and dysregulation of Bax and Bcl-2 gene expression. Whereas, AAS treated MCF-7 cells showed upregulation of Bax and downregulation of Bcl-2 gene expression. AAS treated MCF-7 and SAS cells showed downregulation of Bcl-2 protein expression in comparison to their control cells. Thus, the present study demonstrates that the pro-oxidative effect induced by SS suppresses the cancer growth indicating its potential anticancer activity.

Keywords: Apoptosis; Bax/Bcl-2 dysregulation; Pro-oxidative effect; Silk sericin; p53 upregulation

DOI: https://doi.org/10.1016/j.fct.2018.10.063

Free Radic Biol Med. 2018 Nov 01. pii: S0891-5849(18)31139-0. [Epub ahead of print]

Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and NADPH oxidase activity.

Manoj Paul, Mahadevappa Hemshekhar, Kempaiah Kemparaju, Kesturu S Girish.

Diabetes mellitus (DM) is a serious metabolic disorder affecting millions of people worldwide. The high rate of mortality and morbidity during DM is attributed to the increased atherothrombotic events due to platelet activation and apoptosis leading to macro and micro vascular occlusions. The platelet hyper-reactivity and apoptosis during DM is accounted for the accumulated reactive oxygen species (ROS) due to increased aldose reductase (AR) and NADPH oxidase (NOX) activities. Considering aspirin insensitivity in DM patients, new therapies targeting the underlying mechanism is urgently warranted. Berberine, a benzylisoquinoline alkaloids, from Chinese folk medicine has been demonstrated with several anti-diabetic effects. Therefore, we evaluated whether berberine inhibits high glucose potentiated platelet aggregation, apoptosis and further evaluated the mechanism of its action in platelets. Berberine was found to inhibit platelet aggregation, superoxide production via modulating AR, NOX and glutathione reductase activities in high glucose (HG) treated platelets. Correlated with this, berberine inhibited, calcium release, ERK activation, α- and dense granule release and platelet adhesive properties. In addition, berberine inhibited p38-p53 mediated BAX activation, mitochondrial dysfunction and platelet apoptosis induced by HG. The platelet protective effect of berberine by inhibiting AR and NOX in high glucose treated platelets suggest that berberine could be developed as a potential therapeutic molecule in the treating pathologies associate with DM.

Keywords: Apoptosis; Berberine; Diabetes Mellitus; Platelet aggregation; Platelets

DOI: https://doi.org/10.1016/j.freeradbiomed.2018.10.453

Gene. 2018 Nov 01. pii: S0378-1119(18)31135-1. [Epub ahead of print]685 136-142

MiR-375 induces ROS and apoptosis in ST cells by targeting the HIGD1A gene.

Jia Guo, Chun Yang, Shaoxuan Zhang, Mengdi Liang, Jiajia Qi, Zhenbo Wang, Yinghua Peng, Boxing Sun.

HIGD1A can reduce ROS and apoptosis in cells under low-glucose or hypoxic conditions, and HIGD1A is one of the target genes for miR-375, according to our previous studies. However, it is not known whether miR-375 can indirectly regulate ROS and apoptosis in porcine Sertoli cells. To answer this question, HIGD1A and miR-375 were overexpressed in porcine Sertoli cells, and ROS and apoptosis were assayed. The results showed that ROS levels and expression levels of CASPASE3 in HIGD1A-overexpressing cells were significantly lower than those in the control cells. However, ROS levels and CASPASE3 expression in miR-375-overexpressing cells were significantly higher than those in the control cells. The rate of apoptosis in HIGD1A-overexpressing cells was significantly lower than that in miR-375-overexpressing cells. Considering that the HIGD1A gene is a target of miR-375, these findings suggest that miR-375 can induce an increase in ROS levels and apoptosis by inhibiting HIGD1A in porcine ST cells.

Keywords: Apoptosis; HIGD1A; ROS; ST cells; miR-375

DOI: https://doi.org/10.1016/j.gene.2018.10.086

Biochimie. 2018 Nov 01. pii: S0300-9084(18)30304-3. [Epub ahead of print]157 1-9

Cytotoxic action of acetate on tumor cells of thymic origin: Role of MCT-1, pH homeostasis and altered cell survival regulation.

Shrish Kumar Pandey, Saveg Yadav, Yugal Goel, Sukh Mahendra Singh.

Neoplastic cells display altered biosynthetic and bioenergetic machinery to support cell survival. Therefore, cancer cells optimally utilize all available fuel resources to pump their highly upregulated metabolic pathways. While glucose is the main carbon source, transformed cells also utilize other molecules, which can be utilized in metabolic pathways, designated as alternative fuels. Acetate is one of such alternative metabolic fuels, which is mainly consumed in carbohydrate and lipid metabolism. However, studies demonstrate the contradictory effects of acetate on tumor cell survival. Moreover, the mechanisms of its antitumor actions remain poorly understood. Further, the spectrum of acetate susceptible tumor targets needs to be characterized in order to optimize the use of acetate in maneuvering tumor progression as a therapeutic strategy. As the effect of acetate on survival properties of the tumor cells of thymic origin is not worked out, in the present study the effect of acetate was investigated against tumor cells derived from a murine thymoma designated as Dalton's Lymphoma (DL). Acetate treatment of tumor cells inhibited tumor cell survival accompanied by induction of apoptotic cell death, associated with modulated expression of cell survival regulatory HIF1α, ROS, p53, Caspase 3, Bax and HSP70 along with the elevated level of cytosolic cytochrome c. Acetate treatment also modulated the expression of pH regulators MCT-1 and V-ATPase accompanied by altered pH homeostasis. Expression of MDR and lipid metabolism regulatory molecules was also inhibited in tumor cells upon acetate exposure. Further, pre-exposure of tumor cells to α-CHC (α-cyano-4-hydroxycinnamate), an inhibitor of MCT-1, partially abrogated the cytotoxic action of acetate. These findings shed a new light regarding the effect and mechanisms of the exogenous acetate on the biology of tumor cells of thymic origin.

Keywords: Acetate; Cytotoxicity; MCT-1; Thymoma; pH homeostasis; α-CHC

DOI: https://doi.org/10.1016/j.biochi.2018.10.022